ID   IYD1_HUMAN              Reviewed;         289 AA.
AC   Q6PHW0; C9JFW2; Q2VPW0; Q2VPW1; Q5F1L5; Q5F1L6; Q5THM4; Q6ZP69; Q7Z7D7;
AC   Q7Z7D8;
DT   04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT   04-APR-2006, sequence version 2.
DT   27-MAR-2024, entry version 162.
DE   RecName: Full=Iodotyrosine deiodinase 1 {ECO:0000303|PubMed:25395621};
DE            Short=IYD-1 {ECO:0000303|PubMed:25395621};
DE            EC=1.21.1.1 {ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651, ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
DE   AltName: Full=Iodotyrosine dehalogenase 1 {ECO:0000303|PubMed:15289438, ECO:0000303|Ref.2};
GN   Name=IYD {ECO:0000303|PubMed:25395621};
GN   Synonyms=C6orf71, DEHAL1 {ECO:0000303|PubMed:15289438};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 4 AND 5).
RC   TISSUE=Thyroid;
RA   Moreno J.C., Keijser R., Aarraas S., De Vijlder J.J.M., Ris-Stalpers C.;
RT   "Cloning and characterization of a novel thyroidal gene encoding proteins
RT   with a conserved nitroreductase domain.";
RL   J. Endocrinol. Invest. 25 Suppl. 7:S23-S23(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6).
RC   TISSUE=Thyroid;
RA   Gnidehou S., Ohayon R., Kaniewski J., Morand S., Noel-Hudson M.-S.,
RA   Virion A., Dupuy C.;
RT   "Cloning and characterization of the human iodotyrosine dehalogenase
RT   isoform 1C.";
RL   Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 7).
RC   TISSUE=Thyroid;
RA   Rodrigues-Serpa A.R., Laires R.S., Monteiro C.;
RT   "New transcript variants of the human iodotyrosine dehalogenase gene.";
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-260.
RC   TISSUE=Kidney;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 11-289 (ISOFORM 1).
RC   TISSUE=Kidney;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [7]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP   SPECIFICITY, AND SUBCELLULAR LOCATION.
RX   PubMed=15289438; DOI=10.1096/fj.04-2023fje;
RA   Gnidehou S., Caillou B., Talbot M., Ohayon R., Kaniewski J.,
RA   Noel-Hudson M.-S., Morand S., Agnangji D., Sezan A., Courtin F., Virion A.,
RA   Dupuy C.;
RT   "Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved
RT   in the recycling of iodide close to the thyroglobulin iodination site.";
RL   FASEB J. 18:1574-1576(2004).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=28157283; DOI=10.1021/acs.biochem.6b01308;
RA   Ingavat N., Kavran J.M., Sun Z., Rokita S.E.;
RT   "Active Site Binding Is Not Sufficient for Reductive Deiodination by
RT   Iodotyrosine Deiodinase.";
RL   Biochemistry 56:1130-1139(2017).
RN   [10] {ECO:0007744|PDB:4TTB, ECO:0007744|PDB:4TTC}
RP   X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 32-289 IN COMPLEX WITH
RP   3-IODO-L-TYROSINE AND FMN, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND
RP   SUBUNIT.
RX   PubMed=25395621; DOI=10.1074/jbc.m114.605964;
RA   Hu J., Chuenchor W., Rokita S.E.;
RT   "A switch between one- and two-electron chemistry of the human flavoprotein
RT   iodotyrosine deiodinase is controlled by substrate.";
RL   J. Biol. Chem. 290:590-600(2015).
RN   [11]
RP   VARIANTS TDH4 TRP-101; 105-PHE-ILE-106 DELINS LEU AND THR-116,
RP   CHARACTERIZATION OF VARIANTS TDH4 TRP-101; 105-PHE-ILE-106 DELINS LEU AND
RP   THR-116, MUTAGENESIS OF ARG-101; PHE-105 AND ILE-116, CATALYTIC ACTIVITY,
RP   AND FUNCTION.
RX   PubMed=18434651; DOI=10.1056/nejmoa0706819;
RA   Moreno J.C., Klootwijk W., van Toor H., Pinto G., D'Alessandro M.,
RA   Leger A., Goudie D., Polak M., Grueters A., Visser T.J.;
RT   "Mutations in the iodotyrosine deiodinase gene and hypothyroidism.";
RL   N. Engl. J. Med. 358:1811-1818(2008).
CC   -!- FUNCTION: Catalyzes the dehalogenation of halotyrosines such as 3-
CC       bromo-L-tyrosine, 3-chloro-L-tyrosine, 3-iodo-L-tyrosine and 3,5-
CC       diiodo-L-tyrosine (PubMed:15289438, PubMed:18434651, PubMed:25395621,
CC       PubMed:28157283). During thyroid hormone biosynthesis, facilitates
CC       iodide salvage by catalysing the oxidative NADPH-dependent deiodination
CC       of the halogenated by-products of thyroid hormone production,
CC       monoiodotyrosine (L-MIT) and diiodotyrosine (L-DIT) (PubMed:15289438,
CC       PubMed:18434651). The scavanged iodide can then reenter the hormone-
CC       producing pathways (PubMed:15289438, PubMed:18434651). Acts more
CC       efficiently on 3-iodo-L-tyrosine than 3,5-diiodo-L-tyrosine
CC       (PubMed:15289438). {ECO:0000269|PubMed:15289438,
CC       ECO:0000269|PubMed:18434651, ECO:0000269|PubMed:25395621,
CC       ECO:0000269|PubMed:28157283}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 iodide + L-tyrosine + 2 NADP(+) = 3,5-diiodo-L-tyrosine +
CC         H(+) + 2 NADPH; Xref=Rhea:RHEA:32479, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16382, ChEBI:CHEBI:57506, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58315, ChEBI:CHEBI:58349; EC=1.21.1.1;
CC         Evidence={ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651,
CC         ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:32481;
CC         Evidence={ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651,
CC         ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=iodide + L-tyrosine + NADP(+) = 3-iodo-L-tyrosine + NADPH;
CC         Xref=Rhea:RHEA:27453, ChEBI:CHEBI:16382, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58315, ChEBI:CHEBI:58349, ChEBI:CHEBI:59898;
CC         Evidence={ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651,
CC         ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:27455;
CC         Evidence={ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651,
CC         ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3-iodo-L-tyrosine + iodide + NADP(+) = 3,5-diiodo-L-tyrosine +
CC         H(+) + NADPH; Xref=Rhea:RHEA:27457, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16382, ChEBI:CHEBI:57506, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349, ChEBI:CHEBI:59898;
CC         Evidence={ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651,
CC         ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:27459;
CC         Evidence={ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651,
CC         ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride + L-tyrosine + NADP(+) = 3-chloro-L-tyrosine + NADPH;
CC         Xref=Rhea:RHEA:70343, ChEBI:CHEBI:17996, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58315, ChEBI:CHEBI:58349, ChEBI:CHEBI:189422;
CC         Evidence={ECO:0000269|PubMed:25395621};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70345;
CC         Evidence={ECO:0000269|PubMed:25395621};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=bromide + L-tyrosine + NADP(+) = 3-bromo-L-tyrosine + NADPH;
CC         Xref=Rhea:RHEA:70347, ChEBI:CHEBI:15858, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58315, ChEBI:CHEBI:58349, ChEBI:CHEBI:189423;
CC         Evidence={ECO:0000269|PubMed:25395621};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70349;
CC         Evidence={ECO:0000269|PubMed:25395621};
CC   -!- COFACTOR:
CC       Name=FMN; Xref=ChEBI:CHEBI:58210;
CC         Evidence={ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=2.67 uM for L-DIT {ECO:0000269|PubMed:15289438};
CC         KM=1.35 uM for L-MIT {ECO:0000269|PubMed:15289438};
CC         KM=7.3 uM for 3-iodo-L-tyrosine (at pH 7.4 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:28157283};
CC         KM=4.1 mM for 2-iodophenol (at pH 7.4 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:28157283};
CC         Note=kcat is 0.102 sec(-1) for the dehalogenation of
CC         3-iodo-L-tyrosine (at pH 7.4 and 25 degrees Celsius)
CC         (PubMed:28157283). kcat is 0.004 sec(-1) for the dehalogenation of
CC         2-iodophenol (at pH 7.4 and 25 degrees Celsius) (PubMed:28157283).
CC         {ECO:0000269|PubMed:28157283};
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:25395621}.
CC   -!- INTERACTION:
CC       Q6PHW0; Q86WT6: TRIM69; NbExp=3; IntAct=EBI-10253668, EBI-749955;
CC       Q6PHW0; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-10253668, EBI-11525489;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15289438};
CC       Single-pass membrane protein {ECO:0000269|PubMed:15289438}. Cytoplasmic
CC       vesicle membrane {ECO:0000269|PubMed:15289438}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=6;
CC       Name=1;
CC         IsoId=Q6PHW0-1; Sequence=Displayed;
CC       Name=3; Synonyms=E;
CC         IsoId=Q6PHW0-3; Sequence=VSP_017809, VSP_017810;
CC       Name=4; Synonyms=B;
CC         IsoId=Q6PHW0-4; Sequence=VSP_017805;
CC       Name=5; Synonyms=C;
CC         IsoId=Q6PHW0-5; Sequence=VSP_017806, VSP_017813;
CC       Name=6; Synonyms=D;
CC         IsoId=Q6PHW0-6; Sequence=VSP_017807, VSP_017812;
CC       Name=7; Synonyms=F;
CC         IsoId=Q6PHW0-7; Sequence=VSP_017802, VSP_017803, VSP_017809,
CC                                  VSP_017810;
CC   -!- TISSUE SPECIFICITY: Expressed at a high level in thyroid gland (at
CC       protein level). Expressed at a high level in thyroid gland and at lower
CC       level in kidney and trachea. {ECO:0000269|PubMed:15289438}.
CC   -!- DISEASE: Thyroid dyshormonogenesis 4 (TDH4) [MIM:274800]: A disorder
CC       due to thyroid dyshormonogenesis, causing severe hypothyroidism,
CC       goiter, excessive levels of iodotyrosine in serum and urine, and
CC       variable mental deficits derived from unrecognized and untreated
CC       hypothyroidism. {ECO:0000269|PubMed:18434651}. Note=The disease is
CC       caused by variants affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the nitroreductase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAY41467.1; Type=Erroneous translation; Evidence={ECO:0000305};
CC       Sequence=BAC85255.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AY259176; AAP22072.1; -; mRNA.
DR   EMBL; AY259177; AAP22073.1; -; mRNA.
DR   EMBL; AY424901; AAR84259.1; -; mRNA.
DR   EMBL; AY424902; AAR84260.1; -; mRNA.
DR   EMBL; AY957659; AAY41465.1; -; mRNA.
DR   EMBL; AY957660; AAY41466.1; -; mRNA.
DR   EMBL; AY957661; AAY41467.1; ALT_SEQ; mRNA.
DR   EMBL; AL031010; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC056253; AAH56253.1; -; mRNA.
DR   EMBL; AK129950; BAC85255.1; ALT_INIT; mRNA.
DR   CCDS; CCDS5227.1; -. [Q6PHW0-1]
DR   CCDS; CCDS55066.1; -. [Q6PHW0-3]
DR   CCDS; CCDS55067.1; -. [Q6PHW0-4]
DR   RefSeq; NP_001158166.1; NM_001164694.1. [Q6PHW0-4]
DR   RefSeq; NP_001158167.1; NM_001164695.1. [Q6PHW0-3]
DR   RefSeq; NP_001305424.1; NM_001318495.1.
DR   RefSeq; NP_981932.1; NM_203395.2. [Q6PHW0-1]
DR   PDB; 4TTB; X-ray; 2.45 A; A/B=32-289.
DR   PDB; 4TTC; X-ray; 2.65 A; A/B/C/D/E/F=32-289.
DR   PDB; 5YAK; X-ray; 2.30 A; A/B/C/D/E/F=32-289.
DR   PDBsum; 4TTB; -.
DR   PDBsum; 4TTC; -.
DR   PDBsum; 5YAK; -.
DR   AlphaFoldDB; Q6PHW0; -.
DR   SMR; Q6PHW0; -.
DR   BioGRID; 133150; 11.
DR   IntAct; Q6PHW0; 4.
DR   STRING; 9606.ENSP00000229447; -.
DR   BindingDB; Q6PHW0; -.
DR   DrugBank; DB03374; 3,5-Diiodotyrosine.
DR   GlyGen; Q6PHW0; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q6PHW0; -.
DR   PhosphoSitePlus; Q6PHW0; -.
DR   BioMuta; IYD; -.
DR   DMDM; 91207083; -.
DR   jPOST; Q6PHW0; -.
DR   MassIVE; Q6PHW0; -.
DR   PaxDb; 9606-ENSP00000229447; -.
DR   PeptideAtlas; Q6PHW0; -.
DR   ProteomicsDB; 10043; -.
DR   ProteomicsDB; 67128; -. [Q6PHW0-1]
DR   ProteomicsDB; 67129; -. [Q6PHW0-3]
DR   ProteomicsDB; 67130; -. [Q6PHW0-4]
DR   ProteomicsDB; 67131; -. [Q6PHW0-5]
DR   ProteomicsDB; 67132; -. [Q6PHW0-6]
DR   ProteomicsDB; 67133; -. [Q6PHW0-7]
DR   Antibodypedia; 33325; 80 antibodies from 20 providers.
DR   DNASU; 389434; -.
DR   Ensembl; ENST00000229447.9; ENSP00000229447.5; ENSG00000009765.15. [Q6PHW0-4]
DR   Ensembl; ENST00000344419.8; ENSP00000343763.4; ENSG00000009765.15. [Q6PHW0-1]
DR   Ensembl; ENST00000367335.7; ENSP00000356304.3; ENSG00000009765.15. [Q6PHW0-3]
DR   Ensembl; ENST00000392256.6; ENSP00000376085.2; ENSG00000009765.15. [Q6PHW0-3]
DR   GeneID; 389434; -.
DR   KEGG; hsa:389434; -.
DR   MANE-Select; ENST00000344419.8; ENSP00000343763.4; NM_203395.3; NP_981932.1.
DR   UCSC; uc003qnu.3; human. [Q6PHW0-1]
DR   AGR; HGNC:21071; -.
DR   CTD; 389434; -.
DR   DisGeNET; 389434; -.
DR   GeneCards; IYD; -.
DR   HGNC; HGNC:21071; IYD.
DR   HPA; ENSG00000009765; Tissue enriched (thyroid).
DR   MalaCards; IYD; -.
DR   MIM; 274800; phenotype.
DR   MIM; 612025; gene.
DR   neXtProt; NX_Q6PHW0; -.
DR   OpenTargets; ENSG00000009765; -.
DR   Orphanet; 95716; Familial thyroid dyshormonogenesis.
DR   PharmGKB; PA162392352; -.
DR   VEuPathDB; HostDB:ENSG00000009765; -.
DR   eggNOG; KOG3936; Eukaryota.
DR   GeneTree; ENSGT00390000004348; -.
DR   HOGENOM; CLU_070764_1_1_1; -.
DR   InParanoid; Q6PHW0; -.
DR   OMA; GANHQPW; -.
DR   OrthoDB; 5390904at2759; -.
DR   PhylomeDB; Q6PHW0; -.
DR   TreeFam; TF313415; -.
DR   BioCyc; MetaCyc:ENSG00000009765-MONOMER; -.
DR   BRENDA; 1.21.1.1; 2681.
DR   PathwayCommons; Q6PHW0; -.
DR   Reactome; R-HSA-209968; Thyroxine biosynthesis.
DR   SABIO-RK; Q6PHW0; -.
DR   SignaLink; Q6PHW0; -.
DR   SIGNOR; Q6PHW0; -.
DR   BioGRID-ORCS; 389434; 156 hits in 1144 CRISPR screens.
DR   ChiTaRS; IYD; human.
DR   GeneWiki; Iodotyrosine_deiodinase; -.
DR   GenomeRNAi; 389434; -.
DR   Pharos; Q6PHW0; Tbio.
DR   PRO; PR:Q6PHW0; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; Q6PHW0; Protein.
DR   Bgee; ENSG00000009765; Expressed in right lobe of thyroid gland and 92 other cell types or tissues.
DR   ExpressionAtlas; Q6PHW0; baseline and differential.
DR   GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0010181; F:FMN binding; IDA:UniProtKB.
DR   GO; GO:0140616; F:iodotyrosine deiodinase activity; IDA:UniProtKB.
DR   GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR   GO; GO:0042403; P:thyroid hormone metabolic process; IDA:UniProtKB.
DR   GO; GO:0006570; P:tyrosine metabolic process; IDA:UniProtKB.
DR   CDD; cd02144; iodotyrosine_dehalogenase; 1.
DR   DisProt; DP01741; -.
DR   Gene3D; 3.40.109.10; NADH Oxidase; 1.
DR   InterPro; IPR029479; Nitroreductase.
DR   InterPro; IPR000415; Nitroreductase-like.
DR   PANTHER; PTHR23026:SF90; IODOTYROSINE DEIODINASE 1; 1.
DR   PANTHER; PTHR23026; NADPH NITROREDUCTASE; 1.
DR   Pfam; PF00881; Nitroreductase; 1.
DR   SUPFAM; SSF55469; FMN-dependent nitroreductase-like; 1.
DR   Genevisible; Q6PHW0; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane;
KW   Congenital hypothyroidism; Cytoplasmic vesicle; Disease variant;
KW   Flavoprotein; FMN; Membrane; NADP; Oxidoreductase; Reference proteome;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..289
FT                   /note="Iodotyrosine deiodinase 1"
FT                   /id="PRO_0000230278"
FT   TRANSMEM        1..21
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          29..69
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        29..58
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         100..104
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000269|PubMed:25395621,
FT                   ECO:0007744|PDB:4TTB, ECO:0007744|PDB:4TTC"
FT   BINDING         128..129
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:Q9DCX8"
FT   BINDING         128
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000269|PubMed:25395621,
FT                   ECO:0007744|PDB:4TTC"
FT   BINDING         130
FT                   /ligand="3-iodo-L-tyrosine"
FT                   /ligand_id="ChEBI:CHEBI:59898"
FT                   /evidence="ECO:0007744|PDB:4TTC"
FT   BINDING         157
FT                   /ligand="3-iodo-L-tyrosine"
FT                   /ligand_id="ChEBI:CHEBI:59898"
FT                   /evidence="ECO:0000269|PubMed:25395621,
FT                   ECO:0007744|PDB:4TTC"
FT   BINDING         161
FT                   /ligand="3-iodo-L-tyrosine"
FT                   /ligand_id="ChEBI:CHEBI:59898"
FT                   /evidence="ECO:0000269|PubMed:25395621,
FT                   ECO:0007744|PDB:4TTC"
FT   BINDING         182
FT                   /ligand="3-iodo-L-tyrosine"
FT                   /ligand_id="ChEBI:CHEBI:59898"
FT                   /evidence="ECO:0000269|PubMed:25395621,
FT                   ECO:0007744|PDB:4TTC"
FT   BINDING         237..239
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000269|PubMed:25395621,
FT                   ECO:0007744|PDB:4TTB, ECO:0007744|PDB:4TTC"
FT   BINDING         279
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000269|PubMed:25395621,
FT                   ECO:0007744|PDB:4TTB, ECO:0007744|PDB:4TTC"
FT   VAR_SEQ         1..55
FT                   /note="Missing (in isoform 7)"
FT                   /evidence="ECO:0000303|Ref.3"
FT                   /id="VSP_017802"
FT   VAR_SEQ         56..61
FT                   /note="QAEEDA -> MKEADV (in isoform 7)"
FT                   /evidence="ECO:0000303|Ref.3"
FT                   /id="VSP_017803"
FT   VAR_SEQ         230..289
FT                   /note="NAGLVTVTTTPLNCGPRLRVLLGRPAHEKLLMLLPVGYPSKEATVPDLKRKP
FT                   LDQIMVTV -> VNNGITMRHQTARHRHLIEGPGRSSEACSKLSSQGCPECRSGDCHYH
FT                   SSQLWPSTEGAPGPPRT (in isoform 4)"
FT                   /evidence="ECO:0000303|Ref.1"
FT                   /id="VSP_017805"
FT   VAR_SEQ         230..284
FT                   /note="NAGLVTVTTTPLNCGPRLRVLLGRPAHEKLLMLLPVGYPSKEATVPDLKRKP
FT                   LDQ -> VNNGITMRHQTARHRHLIEGPGRSSEACSKLSSQGRPGASAAGSLFHFAIEF
FT                   AAP (in isoform 5)"
FT                   /evidence="ECO:0000303|Ref.1"
FT                   /id="VSP_017806"
FT   VAR_SEQ         230..270
FT                   /note="NAGLVTVTTTPLNCGPRLRVLLGRPAHEKLLMLLPVGYPSK -> VNNGITM
FT                   RHQTARHRHLIEGPGRSSEACSKLSSQGRPGFYC (in isoform 6)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_017807"
FT   VAR_SEQ         230..248
FT                   /note="NAGLVTVTTTPLNCGPRLR -> VFGKIILKELALISFLNL (in
FT                   isoform 3 and isoform 7)"
FT                   /evidence="ECO:0000303|Ref.3"
FT                   /id="VSP_017809"
FT   VAR_SEQ         249..289
FT                   /note="Missing (in isoform 3 and isoform 7)"
FT                   /evidence="ECO:0000303|Ref.3"
FT                   /id="VSP_017810"
FT   VAR_SEQ         271..289
FT                   /note="Missing (in isoform 6)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_017812"
FT   VAR_SEQ         285..289
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000303|Ref.1"
FT                   /id="VSP_017813"
FT   VARIANT         101
FT                   /note="R -> W (in TDH4; strongly reduces activity; does not
FT                   respond to the increase of flavin mononucleotide
FT                   concentration; dbSNP:rs121918138)"
FT                   /evidence="ECO:0000269|PubMed:18434651"
FT                   /id="VAR_045963"
FT   VARIANT         105..106
FT                   /note="FI -> L (in TDH4; strongly reduces activity; does
FT                   not respond to the increase of flavin mononucleotide
FT                   concentration)"
FT                   /evidence="ECO:0000269|PubMed:18434651"
FT                   /id="VAR_045964"
FT   VARIANT         116
FT                   /note="I -> T (in TDH4; strongly reduces activity;
FT                   marginally respond to the increase of flavin mononucleotide
FT                   concentration; reduces protein stability;
FT                   dbSNP:rs121918139)"
FT                   /evidence="ECO:0000269|PubMed:18434651"
FT                   /id="VAR_045965"
FT   VARIANT         260
FT                   /note="L -> P (in dbSNP:rs17854906)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_025785"
FT   VARIANT         271
FT                   /note="E -> K (in dbSNP:rs36063028)"
FT                   /id="VAR_045966"
FT   MUTAGEN         101
FT                   /note="R->A: Strongly reduces activity."
FT                   /evidence="ECO:0000269|PubMed:18434651"
FT   MUTAGEN         101
FT                   /note="R->H: Reduces activity."
FT                   /evidence="ECO:0000269|PubMed:18434651"
FT   MUTAGEN         105
FT                   /note="F->A: Activity as the wild type."
FT                   /evidence="ECO:0000269|PubMed:18434651"
FT   MUTAGEN         105
FT                   /note="F->Y: Activity as the wild type."
FT                   /evidence="ECO:0000269|PubMed:18434651"
FT   MUTAGEN         116
FT                   /note="I->V: Activity as the wild type."
FT                   /evidence="ECO:0000269|PubMed:18434651"
FT   STRAND          73..75
FT                   /evidence="ECO:0007829|PDB:5YAK"
FT   STRAND          77..79
FT                   /evidence="ECO:0007829|PDB:4TTC"
FT   HELIX           83..98
FT                   /evidence="ECO:0007829|PDB:5YAK"
FT   HELIX           113..123
FT                   /evidence="ECO:0007829|PDB:5YAK"
FT   HELIX           129..131
FT                   /evidence="ECO:0007829|PDB:5YAK"
FT   STRAND          135..140
FT                   /evidence="ECO:0007829|PDB:5YAK"
FT   HELIX           143..162
FT                   /evidence="ECO:0007829|PDB:5YAK"
FT   HELIX           167..173
FT                   /evidence="ECO:0007829|PDB:5YAK"
FT   HELIX           174..176
FT                   /evidence="ECO:0007829|PDB:5YAK"
FT   HELIX           184..187
FT                   /evidence="ECO:0007829|PDB:5YAK"
FT   STRAND          189..201
FT                   /evidence="ECO:0007829|PDB:5YAK"
FT   STRAND          207..209
FT                   /evidence="ECO:0007829|PDB:4TTC"
FT   HELIX           213..230
FT                   /evidence="ECO:0007829|PDB:5YAK"
FT   HELIX           244..250
FT                   /evidence="ECO:0007829|PDB:5YAK"
FT   STRAND          257..266
FT                   /evidence="ECO:0007829|PDB:5YAK"
FT   STRAND          273..275
FT                   /evidence="ECO:0007829|PDB:5YAK"
FT   HELIX           282..284
FT                   /evidence="ECO:0007829|PDB:5YAK"
FT   STRAND          286..289
FT                   /evidence="ECO:0007829|PDB:4TTB"
FT   CONFLICT        Q6PHW0-4:265
FT                   /note="C -> R (in Ref. 1; AAP22073)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   289 AA;  33360 MW;  B73560A682BF6045 CRC64;
     MYFLTPILVA ILCILVVWIF KNADRSMEKK KGEPRTRAEA RPWVDEDLKD SSDLHQAEED
     ADEWQESEEN VEHIPFSHNH YPEKEMVKRS QEFYELLNKR RSVRFISNEQ VPMEVIDNVI
     RTAGTAPSGA HTEPWTFVVV KDPDVKHKIR KIIEEEEEIN YMKRMGHRWV TDLKKLRTNW
     IKEYLDTAPI LILIFKQVHG FAANGKKKVH YYNEISVSIA CGILLAALQN AGLVTVTTTP
     LNCGPRLRVL LGRPAHEKLL MLLPVGYPSK EATVPDLKRK PLDQIMVTV
//